Summary/Abstract Recent advances in MR spectroscopic imaging (MRSI), diffusion tensor imaging (DTI) and functional MRI (fMRI) have the potential to enhance the clinical utility of presurgical mapping to aid in the diagnosis, treatment planning and surgical resection of brain neoplasms. Diffusion tensor spectroscopic imaging (DTSI) can provide unique information on intracellular properties, such as viscosity, cell swelling, restriction in subcellular structures, and cytoplasmic streaming that may help to characterize infiltration and inflammatory processes. DTSI complements recently developed Q-space trajectory imaging (QTI) of tissue water, which can measure tumor specific abnormalities in microscopic anisotropy and isotropic heterogeneity not seen in linearly encoded diffusion tensor imaging (DTI). Resting state fMRI (rsfMRI) is a promising task-free whole brain approach complementing task-based fMRI (tfMRI) and extending mapping of eloquent cortex to patients with impairment. Evaluating the individual and joint tissue and functional specificity of these advanced MRSI technologies and their clinical utility for presurgical mapping in patients with brain tumors is of considerable interest. However, integration of DTSI with QTI and fMRI is been hampered by long scan times and motion sensitivity of DTSI, which prevents routine clinical use. The primary objective of this proposal is to develop a method to reduce motion sensitivity of DTSI using single-shot encoding, to integrate DTSI and high-speed fMRI into a single pulse sequence to reduce long scan times in multi-modal presurgical mapping, and to validate this approach in healthy adults and in patients with brain tumors. A secondary objective is to assess the individual and joint sensitivity and specificity of DTSI and QTI for tissue characterization. Our preliminary results using Proton-Echo-Planar-Spectroscopic-Imaging (PEPSI) at 3 Tesla demonstrate (a) the feasibility of mapping the age dependence of metabolite diffusion in children and adults, (b) presurgical mapping with high-speed fMRI and fast short TE 3D MRSI in patients with brain tumors, and (c) proof-of-concept of simultaneous fMRI and MRSI in a single scan. The rationale of this research is that multi-modal presurgical mapping provides complementary biomarkers for improving sensitivity and specificity of characterizing tumor tissue status and tumor boundaries in relation to eloquent cortex, complementing surgical decision making and prediction of functional and oncological outcomes. If successful, this research will promote integration of advanced MRSI into clinical brain mapping protocols to study novel tissue-specific biomarkers and their association with pathology.